Related Experiment Video
Updated: Jan 14, 2026
07:33
Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS
Published on: December 21, 2011
16.0K
Macrophage-derived exosome miR-146a-5p modulates PNKP/DDOST/JAGN1 complex to regulate NETs formation in
Zhen Liu1, Wei Zhang1, Yihang Li1
1Department of Vascular Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
Cellular Signalling
|October 18, 2025
Summary
Macrophage exosomes carrying miR-146a-5p regulate neutrophil extracellular trap (NET) formation via the PNKP/DDOST/JAGN1 pathway, offering new therapeutic targets for atherosclerosis (AS). This discovery sheds light on macrophage-neutrophil interactions in AS progression.
Area of Science:
- Molecular Biology
- Immunology
- Cardiovascular Research
Background:
- Atherosclerosis (AS) progression is linked to neutrophil extracellular trap (NET) formation.
- The precise regulatory interactions between macrophages and neutrophils in AS remain incompletely understood.
Purpose of the Study:
- To elucidate the role of macrophage-derived exosomes in regulating NET formation during atherosclerosis.
- To investigate the specific molecular mechanisms involving miR-146a-5p and its downstream targets.
Main Methods:
- Atherosclerosis model established in ApoE-/- mice.
- Exosomes isolated from oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages.
- Analysis of miR-146a-5p regulation of the PNKP/DDOST/JAGN1 complex using qRT-PCR, Western blot, co-immunoprecipitation, RIP, and dual-luciferase reporter assays.
Main Results:
- Macrophage-derived exosomes showed increased miR-146a-5p, suppressing PNKP and altering DDOST phosphorylation.
- This cascade activated JAGN1-dependent NET formation.
- Inhibition of miR-146a-5p reduced NETs, reactive oxygen species (ROS), plaque burden, and inflammation in AS mice.
Conclusions:
- Macrophage exosome miR-146a-5p regulates NET formation via the PNKP/DDOST/JAGN1 axis.
- This pathway presents a novel mechanism in AS pathogenesis.
- Identified potential therapeutic targets for AS treatment.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
3.2K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.2K
01:24Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K